scholarly journals Differences in Abnormal Water Metabolism between SD Rats and KM Mice Intoxicated by Microcystin-RR

2021 ◽  
Vol 18 (4) ◽  
pp. 1900
Author(s):  
Wenqing Xiao ◽  
Qing Zhong ◽  
Feng Sun ◽  
Weiguang Wang ◽  
Zhiyao Zhao ◽  
...  
Keyword(s):  
Single Dose ◽  
Kidney Injury ◽  
Continuous Exposure ◽  
Sprague Dawley ◽  
Water Metabolism ◽  
Exposure Test ◽  
Histological Changes ◽  
Sd Rats ◽  
Km Mice ◽  
Km Mouse

The effects of microcystin-RR (MC-RR) on water metabolism were studied on Sprague–Dawley (SD) rats and KunMing (KM) mice. In the single dose toxicity test, polydipsia, polyuria, hematuria and proteinuria were found in group of rats receiving a MC-RR dose of 574.7 μg/kg, and could be relieved by dexamethasone (DXM). Gradient damage was observed in kidney and liver in rats with gradient MC-RR doses of 574.7, 287.3, and 143.7 μg/kg. No significant water metabolic changes or kidney injuries were observed in mice treated with MC-RR doses of 210.0, 105.0, and 52.5 μg/kg. In the continuous exposure test, in which mice were administrated with 140.0, 70.0, and 35.0 μg/kg MC-RR for 28 days, mice in the 140.0 μg/kg group presented increasing polydipsia, polyuria, and liver damage. However, no anatomic or histological changes, including related serological and urinary indices, were found in the kidney. In summary, abnormal water metabolism can be induced by MC-RR in rats through kidney injury in single dose exposure; the kidney of SD rats is more sensitive to MC-RR than that of KM mouse; and polydipsia and polyuria in mice exposed to MC-RR for 28 days occurred but could not be attributed to kidney damage.

scholarly journals Enhanced renal ischemia-reperfusion injury in aging and diabetes

2018 ◽  
Vol 315 (6) ◽  
pp. F1843-F1854 ◽  
Author(s):  
Yoshikazu Muroya ◽  
Xiaochen He ◽  
Letao Fan ◽  
Shaoxun Wang ◽  
Rui Xu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Sprague Dawley ◽  
Middle Aged ◽  
Sd Rats ◽  
Effects Of Aging

The incidence and severity of acute kidney injury is increased in patients with diabetes and with aging. However, the mechanisms involved have not been clearly established. The present study examined the effects of aging and diabetes on the severity of renal ischemia-reperfusion (IR) injury in Sprague-Dawley (SD) and type 2 diabetic (T2DN) rats. T2DN rats develop diabetes at 3 mo of age and progressive proteinuria and diabetic nephropathy as they age from 6 to 18 mo. Plasma creatinine levels after bilateral IR were significantly higher (3.4 ± 0.1 mg/dl) in 18-mo-old elderly T2DN rats than in middle-aged (12 mo) T2DN rats with less severe diabetic nephropathy or young (3 mo) and elderly (18 mo) control SD rats (1.5 ± 0.2, 1.8 ± 0.1, and 1.7 ± 0.1 mg/dl, respectively). Elderly T2DN rats exhibited a greater fall in medullary blood flow 2 h following renal IR and a more severe and prolonged decline in glomerular filtration rate than middle-aged T2DN and young or elderly SD rats. The basal expression of the adhesion molecules ICAM-1 and E-selectin and the number of infiltrating immune cells was higher in the kidney of elderly T2DN than age-matched SD rats or young and middle-aged T2DN rats before renal IR. These results indicate that elderly T2DN rats with diabetic nephropathy are more susceptible to renal IR injury than diabetic animals with mild injury or age-matched control animals. This is associated with increased expression of ICAM-1, E-selectin and immune cell infiltration, renal medullary vasocongestion, and more prolonged renal medullary ischemia.

scholarly journals Vascular endothelial growth factor receptor inhibitor enhances dietary salt-induced hypertension in Sprague-Dawley rats

2009 ◽  
Vol 297 (1) ◽  
pp. R142-R148 ◽  
Author(s):  
Jian-Wei Gu ◽  
R. Davis Manning ◽  
Emily Young ◽  
Megan Shparago ◽  
Brandi Sartin ◽  
...  
Keyword(s):  
Kidney Injury ◽  
No Production ◽  
Vegf Receptor ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
High Sodium ◽  
Sodium Diet ◽  
Sd Rats ◽  
Induced Hypertension ◽  
Receptor Inhibitor

Clinical evidence links the inhibition of VEGF to hypertension. However, the mechanisms by which VEGF affects the pathogenesis of hypertension remain in question. We determined 1) whether administration of VEGF receptor inhibitor SU5416 enhances dietary salt-induced hypertension in Sprague-Dawley (SD) rats, and 2) whether VEGF or SU5416 directly affects proliferation of cultured human renal proximal tubular epithelial cells (HRPTEC) and endothelial nitric oxide synthase (eNOS) expression in cultured human glomerular microvessel endothelial cells (HGMEC). Ten 10-wk-old male SD rats received a high sodium diet (HS; 8%) and the other 10 SD rats received a normal sodium diet (NS; 0.5%) for 4 wks. After 2 wks of the dietary program, five rats were administered with SU5416 at 10 mg·kg−1·day−1 ip or DMSO (vehicle) for 14 days in HS and NS groups. Mean arterial pressure was significantly higher in rats treated with SU5416, as opposed to those treated with DMSO and fed with HS for 4 wk (157.6 ± 3.9 vs. 125.9 ± 4.3 mmHg, P < 0.01). Increased proteinuria and albuminuria were associated with marked renal histological abnormalities in HS group with SU5416 administration, compared with those in the vehicle HS group. 3H-thymidine incorporation assay showed that SU5416 blocked the actions of both exogenous and endogenous VEGF on the proliferation of HRPTEC. VEGF (10 ng/ml) significantly increased eNOS protein levels by 29% in cultured HGMEC, but its action was completely abolished by SU5416. These results suggest that VEGF receptor inhibition enhances dietary salt-induced hypertension and kidney injury, possibly by direct damage on renal cells and decreasing NO production by eNOS.

scholarly journals Establishment of Simple and Routine Methods in Early Diagnosis of Gentamicin-Induced Kidney Injury Based on a Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Cuiyan Liu ◽  
Youxi Kang ◽  
Huiqin Zhang ◽  
Long Zhu ◽  
Hai Yu ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Kidney Injury ◽  
Transitional Epithelium ◽  
Control Group ◽  
Sprague Dawley ◽  
Special Equipment ◽  
Once Daily ◽  
Sd Rats ◽  
Highly Sensitive ◽  
Blood And Urine Samples

The changes in biomarkers of gentamycin- (GM-) induced kidney injury have been studied by using simple and routine methods and also assessed the efficacy and utility of these routine biomarkers in early diagnosis. Eighty Sprague-Dawley (SD) rats were randomly divided into 4 groups: three experimental groups treated with different GM dosages (4, 20, and 100 mg·kg−1) and a control group. The experimental groups were given intramuscular GM injections once daily for 14 days, and the control group was given intramuscular sterile water. Blood and urine samples were collected on treatment days 1, 3, 7, and 14 to test for total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CRE), uric acid (UA), pH, specific gravity (SG), proteins (PRO), and cells in urinary sediment. Histopathology and kidney coefficient were performed on excised kidney specimens. The result indicated that serum CRE, BUN, and TP, urine PRO, and urinary hyaline casts and low-transitional epithelium showed an immediate and highly sensitive response to kidney injury, and the combined diagnosis with the above methods could be used in early diagnosis. Particularly, the process of the test was simple and quick, no special equipment, so it is more suit for primary medical institution.

Abstract 105: Therapeutic Suppression of Mtorc2 Signaling Reduces Salt-induced Hypertension and Kidney Injury in SS Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Vikash Kumar ◽  
Loiuse Evans ◽  
Clayton Wollner ◽  
Theresa Kurth ◽  
Allen W Cowley
Keyword(s):  
Blood Pressure ◽  
Renal Cortex ◽  
Kidney Injury ◽  
Salt Sensitivity ◽  
Sprague Dawley ◽  
Urine Albumin ◽  
Sd Rats ◽  
Excess Production ◽  
Induced Hypertension

The present study explored the protective effect of mTORC2 inhibition in salt-induced hypertension and kidney injury. We have previously reported that enhanced blood pressure salt-sensitivity with renal chronic interstitial infusion of H 2 O 2 (347 nmol/kg/min) in normotensive Sprague Dawley (SD) rats. In the present study, in vivo experiment was performed in which H 2 O 2 (347 nmol/Kg/min) was chronically infused for 3 days into renal interstitium of unilaterally nephrectomized SD rats. A significant increase of mTORC2 activity (pAKT/AKT) was observed in the renal cortex of SD rats infused with H 2 O 2 compared to saline infused rats. We have recently shown that excess production of H 2 O 2 in the SS rat kidneys is the hallmark of salt-induced hypertension. We hypothesized that mTORC2 in the kidney contributes to the development of salt-induced hypertension in SS rats. Rats were treated with PP242 which is an ATP-competitor inhibitor which inhibits the activities of both mTORC1 and mTORC2 whereas rapamycin specifically inhibits mTORC1. PP242 was administrated daily (i.p., 15 mg/Kg/day) for 21 days to SS rats fed a 4.0% NaCl diet. Remarkably, salt-induced hypertension was significantly reduced in SS rats which averaged 119 ± 2 mmHg in PP242 treated rats (n=7) compared to 168 ± 3 mmHg in vehicle treated rats (n=7). Albuminuria was greatly reduced with urine albumin excretion (mg/day) averaging 32.8 ± 3 in PP242 treated rats compared to 256 ± 37 in vehicle treated rats. PP242 treatment notably resulted in reduced infiltration of T lymphocytes in the kidneys of SS rats fed a 4.0% NaCl diet. CD3 + cells/mm 2 averaging 157.0 ± 40.0 compared to 36.0 ± 11.0 in the renal cortex and 218.0 ± 24.0 compared to 24.0 ± 9.0 in the outer medulla in PP242 versus vehicle treated rats. These data show that mTORC2 is required for the intiation of salt-induced hypertension and therapeutic suppression of this pathway virtually abolished salt-sensitivity blood pressure and kidney injury.

scholarly journals Study on Single-dose Intramuscular Toxicity of Shinbaro Pharmacopuncture in Sprague-Dawley (SD) Rats and Beagle Dogs

2015 ◽  
Vol 25 (3) ◽  
pp. 1-9 ◽  
Author(s):  
Jin-Ho Lee ◽  
Hwa-Jin Chung ◽  
In-Hee Lee ◽  
Jae-Woong Lee ◽  
Eun-Jee Kim ◽  
...  
Keyword(s):  
Single Dose ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Sd Rats

scholarly journals Toxicological Assessment of Bromochlorophene: Single and Repeated-Dose 28-Day Oral Toxicity, Genotoxicity, and Dermal Application in Sprague–Dawley Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Hansol Won ◽  
Da Hye Jeong ◽  
Hyo-Sook Shin ◽  
Jin Hee Lee ◽  
Jeong Pyo Lee ◽  
...  
Keyword(s):  
Single Dose ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Repeated Dose ◽  
High Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Sd Rats ◽  
Dermal Application

Bromochlorophene (BCP) has shown good properties in sterilization and antibacterial activity and is widely used as a household chemical. We evaluated the genotoxicity, single and repeated-dose 28-day oral toxicity, and dermal application of a BCP suspension in Sprague–Dawley (SD) rats. For the single-dose toxicity study, a dose of 25–1,000 mg per kg of bodyweight (mg/kg b.w.) of BCP was given once orally to SD rats. Mortality and clinical signs were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. For the repeated-dose 28-day toxicity study, the high dose was set at 1,000 mg/kg b.w. and the middle, middle-low, and low dose were set to 500, 250, and 125 mg/kg, respectively. Hematology and biochemistry parameters were examined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. A bacterial reverse mutation assay, in vitro chromosomal aberration assay, and in vivo micronucleus assay were performed to assess genotoxicity-dermal application exposure assessment of BCP in rats. A high oral approximate lethal dose (ALD) of 1,000 mg/kg was observed in the single-dose toxicity test. During the repeated-dose 28-day time period, most animal deaths after administration occurred during the first 3 weeks. The 1,000 mg/kg b.w. oral dose caused the death of six male rats (6/7) and four female rats (4/7). At 500 mg/kg b.w., the female rats showed mortality (1/7). For the biochemistry assays, cholesterol was increased significantly compared to vehicle in both sexes in the 250 and 500 mg/kg groups. Histopathological changes with treatment-related findings were observed in the pancreas in female rats treated with a high dose of BCP compared with the vehicle group. BCP showed no genotoxic effect. These data suggested that the ALD of BCP, estimated as a non-genotoxic substance, was over 1,000 mg/kg b.w. in the single-dose toxicity study, and the NOAEL of BCP was considered to be 250 mg/kg b.w. for male and female rats after repeated oral administration for 28 days under the present study conditions.

scholarly journals The long-term bio-behavioural effects of juvenile sildenafil treatment in Sprague-Dawley versus Flinders Sensitive Line rats

2021 ◽  
pp. 1-20
Author(s):  
Juandré Lambertus Bernardus Saayman ◽  
Stephanus Frederik Steyn ◽  
Christiaan Beyers Brink
Keyword(s):  
Sprague Dawley ◽  
Long Term Effects ◽  
Bdnf Level ◽  
Treatment Groups ◽  
Sd Rats ◽  
Behavioural Effects ◽  
Sensitive Line ◽  
Level Analysis ◽  
Flinders Sensitive Line

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

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